HIV-1 Infection is associated with adverse outcomes in endocrine systems. Illicit drug abuse is a major risk factor for contracting HIV-1 infection and is also associated with abnormal endocrine outcomes. Several studies including ours have reported exacerbated endocrine abnormalities among drug abusing HIV-1+ individuals. But these investigations have been carried out among cocaine and/or opioids addicts, and the culture of drug abuse in the United States is changing. Methamphetamine (meth) is becoming a drug of choice all over the country and its abuse in South Florida particularly among MSM has skyrocketed. There is, however, a scarcity of investigations on the impact of methamphetamine on endocrines in HIV-1 infection. It is hypothesized that adrenal activity will be increased, there will be a hyper activity of thyroid as well as an increased incidence of insulin resistance, among HIV-1+ meth abusing MSM. In order to test these hypotheses, this 5 year application proposes to investigate cross sectionally adrenal, thyroid, and insulin activity in a total of 450 men in three groups: HIV-1+ meth abusers (n=150), HIV-1- meth abusers (n=150), HIV-1 - non-meth abusers (n=150) distributed among African Americans, Caucasians, and Hispanics. Because of the planned focus on MSM, only men will be included in the study. The following are aims: Aim 1: To investigate adrenal activity (ACTH and cortisol levels) as well as response to the combined dexamethasone-CRH challenge among meth abusing-HIV-1+ MSM, meth abusing HIV-1- MSM and HIV-1- meth-free control participants. Aim 2: To investigate thyroid activity (TSH, T4 and T3) as well as thyroid antibodies among meth abusing-HIV-1+ MSM, meth abusing HIV-1- MSM and HIV-1- meth-free control participants. Aim 3: To explore insulin activity among meth abusing-HIV-1+ MSM;meth abusing HIV-1- MSM and HIV-1- meth-free control participants. These endocrine disturbances may lead to enormous burden of a number of serious medical consequences and outcomes in meth abusing MSM and further allow developing suitable interventions. PUBLIC HEALTH RELEVANCE: Methamphetamine (meth) abuse particularly among MSM in South Florida has skyrocketed. Although endocrine outcomes in HIV-1 infection as well as drug abusers with HIV- 1 infection have been investigated, there is scarcity of information regarding such outcomes in HIV-1+ meth abusing MSM. This proposal investigates adrenal, thyroid and insulin activities in this population. It is proposed that adverse endocrine outcomes may result in an enormous medical burden.